7. PROJECT SUMMARY/ABSTRACT Specific aims: There are three aims for the proposed research: 1a) To describe the cumulative incidence of breast cancer in women with antiretroviral treated HIV in 2000-2017, stratified by calendar time (2000-2005, 2006-2011, 2012-2017); 1b) To estimate the risk of breast cancer in women with antiretroviral treated HIV comparing women with high versus low viral load in 2007-2017 by sociodemographic factors; 2) To estimate differences in estrogen (estradiol) in pre and perimenopausal women with versus without HIV, and by HIV viral load among women with HIV (WHIV); 3) To determine the association between circulating estradiol and the risk of postmenopausal breast cancer in women with and without HIV. Significance: These three aims will provide novel evidence on the etiology of breast cancer, and whether HIV could play a role in cancer development. If sociodemographic differences between women with and without HIV contribute substantially to the reduced risk of breast cancer in WHIV, then the incidence of breast cancer will likely rise in WHIV, which has important implications for the clinical management of HIV in women. If HIV infection appears to contribute to this reduced risk, this research will generate hypotheses regarding the role of HIV and immune function in breast cancer etiology and potential novel mechanisms for cancer therapy. Approach: Data sources include two large, prospective cohort studies, capturing validated cancer diagnoses and relevant covariates. For Aim 1a and 1b, we will use the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) to characterize the cumulative incidence of breast cancer and its association with viral load in WHIV. The study population for Aims 2 and 3 will be the Women?s Interagency HIV Study (WIHS). For Aim 2, pre and perimenopausal women with pre-existing estradiol measurements will be utilized to assess the relationship between HIV status and estradiol, and among WHIV, the relationship between HIV viral load and estradiol. For Aim 3, a nested case-control study among postmenopausal women in the WIHS will be conducted to evaluate the relationship between HIV and estradiol on breast cancer risk. Fellowship training: Sally Coburn is a PhD student in the Department of Epidemiology at the Johns Hopkins Bloomberg School of Public Health. The proposed research encompasses her dissertation research, which will be conducted in collaboration with the selected sponsor and three mentors offering distinct content expertise. This research is nested within a larger, comprehensive training program including coursework as well as opportunities for teaching and professional development.